Abstract
Background and aimsAbnormal glucagon secretion and functional alterations of the exocrine pancreas have been described in patients with type 1 diabetes (T1D), but their respective anatomical substrata have seldom been investigated. Our aim was to develop an automated morphometric analysis process to characterize the anatomy of α-cell and exocrine pancreas in patients with T1D, using the publicly available slides of the Network for Pancreatic Organ Donors (nPOD).Materials and methodsThe ratio of β- and α-cell area to total tissue area were quantified in 75 patients with T1D (thereafter patients) and 66 control subjects (thereafter controls), on 2 insulin-stained and 4 glucagon-stained slides from both the head and the tail of the pancreas. The β- and α-cell masses were calculated in the 66 patients and the 50 controls for which the pancreas weight was available. Non-exocrine-non-endocrine tissue area (i.e. non-acinar, non-insular tissue) to total tissue area ratio was evaluated on both insulin- and glucagon-stained slides. Results were expressed as mean ±SD.ResultsAn automated quantification method was set up using the R software and was validated by quantification of β-cell mass, a well characterized parameter. β-cell mass was 29.6±112 mg in patients and 628 ±717 mg in controls (p<0.0001). α-cell mass was 181±176 mg in patients and 349 ±241mg in controls (p<0.0001). Non-exocrine-non-endocrine area to total tissue area ratio was 39±9% in patients and 29± 10% in controls (p<0.0001) and increased with age in both groups, with no correlation with diabetes duration in patients.ConclusionThe absolute α-cell mass was lower in patients compared to controls, in proportion to the decrease in pancreas weight observed in patients. Non-exocrine-non-endocrine area to total tissue area ratio increased with age in both groups but was higher in patients at all ages.
Highlights
Type 1 diabetes (T1D) is the late consequence of a β-cell-targeted autoimmune disease that is thought to spare other endocrine and exocrine cell types of the pancreas
Abnormal glucagon secretion and functional alterations of the exocrine pancreas have been described in patients with type 1 diabetes (T1D), but their respective anatomical substrata have seldom been investigated
Functional alterations in glucagon secretion have long been described in T1D, including hyperglucagonemia, which may contribute to hyperglycemia [1,2,3,4] and to decreased glucagon secretion in response to hypoglycemia [5,6]
Summary
Type 1 diabetes (T1D) is the late consequence of a β-cell-targeted autoimmune disease that is thought to spare other endocrine and exocrine cell types of the pancreas. The exocrine pancreas is both anatomically and functionally affected in longstanding T1D [11,12,13,14,15], but the causes of exocrine alterations are poorly understood. This raises the question whether the β-cell specific disease of T1D may later affect the pancreas as a whole. Our aim was to develop an automated morphometric analysis process to characterize the anatomy of α-cell and exocrine pancreas in patients with T1D, using the publicly available slides of the Network for Pancreatic Organ Donors (nPOD)
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